RTOG versus CTCAE score: reporting toxicity of HDR brachytherapy Monotherapy for prostate cancer Marjory Jolicoeur1, Elise Hill1. 1CICM Hôpital Charles Le Moyne, Radiation Oncology, Greenfield Park, Canada.
	Purpose or Objective Compare the Radiation Therapy Oncology Group (RTOG) score and the Common Terminology Criteria for Adverse Events (CTCAE) score for reporting toxicities of HDR brachytherapy as monotherapy for prostate cancer. Material and Methods Mixed-method methodology was applied. The mixed-method consisted of direct comparison of the scores, a systematic literature review (25 selected articles), and the comparison of the acute toxicity scores classification in a sample of prostatic cancer patients treated by HDR brachytherapy. The patients included in this study were part of the protocol named: HDR Brachytherapy as Monotherapy for Low and Intermediate Risk Prostate Cancer (BRP2) (https://clinicaltrials.gov/ct2/show/NCT03424694). 168 patients were followed up for 3 months after HDR brachytherapy for low and intermediate risk prostate cancer. Patients were evaluated at 1, 3, 6 weeks and 3 months after radiotherapy. Symptoms were classified according to RTOG and CTCAE scores. Descriptive statistics and Fisher Exact test were used to compare RTOG and CTCAE scores. Statistical significance was 0.05. Results RTOG score unifies several toxicity symptoms in each of the five grades, while CTCAE score classifies each symptom within five grades, according to their severity. RTOG score lacks reproducibility between acute and late toxicities. CTCAE proposes the same score for describing both late and acute toxicities. 64% of the systematic literature review selected studies were prospective. 76% of them used CTCAE, 20% used RTOG, 4% used neither to evaluate early toxicity. There was no standard for the toxicity reporting methodology. 24% of the articles did not report when the toxicity was evaluated. 48% did not inform how the toxicity was evaluated. Only 19% fully reported which symptoms were evaluated. 48% of the studies did not inform if the toxicity was reported per event or worse toxicity per patient. The early toxicity of 168 patients was compared between RTOG and CTCAE scores (Table 1). RTOG classified patients’ genitourinary and gastrointestinal toxicities at higher grade than CTCAE. RTOG and CTCAE scores were associated in all scenarios (p<0.01), even with percentages of ≥ grade 2 toxicities differing.  Conclusion There is no significant statistical difference between the scores, even thought RTOG score tends to increase the severity of the described symptoms. While, CTCAE appears to be more complex it is more reliable and reproductible in research, since each symptom is separately described with its corresponding grade. The use of the CTCAE score is preferable for reporting toxicities of HDR brachytherapy as monotherapy for prostate cancer. Detailed methodology and the use of guidelines can improve research quality, guarantee the report quality, and facilitate future research comparisons.
References

         

Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995 Mar 30;31(5):1341-6. PubMed PMID: 7713792.

National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE). https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm  Access Date: 01/10/2018

Aluwini, S., Busser, W. M. H., Alemayehu, W. G., Boormans, J. L., Kirkels, W. J., Jansen, P. P., . . . Kolkman-Deurloo, I.-K. K. (2015). Toxicity and quality of life after high-dose-rate brachytherapy as monotherapy for low- and intermediate-risk prostate cancer. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 117, 252-257. doi: 10.1016/j.radonc.2015.09.019

Aluwini, S., Busser, W. M. H., Baartman, L. E. A., Bhawanie, A., Alemayehu, W. G., Boormans, J. L., & Kolkman-Deurloo, I.-K. K. (2016). Fractionated high-dose-rate brachytherapy as monotherapy in prostate cancer: Does implant displacement and its correction influence acute and late toxicity? Brachytherapy, 15, 707-713. doi: 10.1016/j.brachy.2016.05.008

Cendales, R., Alwers, E., Cifuentes, J., Bobadilla, I., Torres, F., Arbelaez, J., . . . Vasquez, J. (2015). High-dose-rate brachytherapy delivered in two fractions as monotherapy for low-risk prostate cancer. Journal of contemporary brachytherapy, 7, 10-16. doi: 10.5114/jcb.2015.48838

Demanes, D. J., Martinez, A. A., Ghilezan, M., Hill, D. R., Schour, L., Brandt, D., & Gustafson, G. (2011). High-dose-rate monotherapy: safe and effective brachytherapy for patients with localized prostate cancer. International journal of radiation oncology, biology, physics, 81, 1286-1292. doi: 10.1016/j.ijrobp.2010.10.015

Gaudet, M., Pharand-Charbonneau, M., Desrosiers, M.-P., Wright, D., & Haddad, A. (2018). Early toxicity and health-related quality of life results of high-dose-rate brachytherapy as monotherapy for low and intermediate-risk prostate cancer. Brachytherapy. doi: 10.1016/j.brachy.2018.01.009

Ghadjar, P., Keller, T., Rentsch, C. A., Isaak, B., Behrensmeier, F., Stroux, A., . . . Aebersold, D. M. (2009). Toxicity and early treatment outcomes in low- and intermediate-risk prostate cancer managed by high-dose-rate brachytherapy as a monotherapy. Brachytherapy, 8, 45-51. doi: 10.1016/j.brachy.2008.09.004

Ghilezan, M., Martinez, A., Gustason, G., Krauss, D., Antonucci, J. V., Chen, P., . . . Limbacher, A. (2012). High-dose-rate brachytherapy as monotherapy delivered in two fractions within one day for favorable/intermediate-risk prostate cancer: preliminary toxicity data. International journal of radiation oncology, biology, physics, 83, 927-932. doi: 10.1016/j.ijrobp.2011.05.001

Gomez-Iturriaga, A., Casquero, F., Pijoan, J. I., Minguez, P., Espinosa, J. M., Irasarri, A., . . . Bilbao, P. (2018). Health-related-quality-of-life and toxicity after single fraction 19Gy high-dose-rate prostate brachytherapy: Phase II trial. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 126, 278-282. doi: 10.1016/j.radonc.2017.10.039

Grills, I. S., Martinez, A. A., Hollander, M., Huang, R., Goldman, K., Chen, P. Y., & Gustafson, G. S. (2004). High dose rate brachytherapy as prostate cancer monotherapy reduces toxicity compared to low dose rate palladium seeds. The Journal of urology, 171, 1098-1104. doi: 10.1097/01.ju.0000113299.34404.22

Hoskin, P., Rojas, A., Ostler, P., Hughes, R., Alonzi, R., Lowe, G., & Bryant, L. (2014). High-dose-rate brachytherapy alone given as two or one fraction to patients for locally advanced prostate cancer: acute toxicity. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 110, 268-271. doi: 10.1016/j.radonc.2013.09.025

Jawad, M. S., Dilworth, J. T., Gustafson, G. S., Ye, H., Wallace, M., Martinez, A., . . . Krauss, D. J. (2016). Outcomes Associated With 3 Treatment Schedules of High-Dose-Rate Brachytherapy Monotherapy for Favorable-Risk Prostate Cancer. International journal of radiation oncology, biology, physics, 94, 657-666. doi: 10.1016/j.ijrobp.2015.10.011

Krauss, D. J., Ye, H., Martinez, A. A., Mitchell, B., Sebastian, E., Limbacher, A., & Gustafson, G. S. (2017). Favorable Preliminary Outcomes for Men With Low- and Intermediate-risk Prostate Cancer Treated With 19-Gy Single-fraction High-dose-rate Brachytherapy. International journal of radiation oncology, biology, physics, 97, 98-106. doi: 10.1016/j.ijrobp.2016.08.011

Kukielka, A. M., Dabrowski, T., Walasek, T., Olchawa, A., Kudzia, R., & Dybek, D. (2015). High-dose-rate brachytherapy as a monotherapy for prostate cancer--Single-institution results of the extreme fractionation regimen. Brachytherapy, 14, 359-365. doi: 10.1016/j.brachy.2015.01.004

Mohammed, N., Kestin, L., Ghilezan, M., Krauss, D., Vicini, F., Brabbins, D., . . . Martinez, A. (2012). Comparison of acute and late toxicities for three modern high-dose radiation treatment techniques for localized prostate cancer. International journal of radiation oncology, biology, physics, 82, 204-212. doi: 10.1016/j.ijrobp.2010.10.009

Morton, G., Chung, H. T., McGuffin, M., Helou, J., D'Alimonte, L., Ravi, A., . . . Loblaw, A. (2017). Prostate high dose-rate brachytherapy as monotherapy for low and intermediate risk prostate cancer: Early toxicity and quality-of life results from a randomized phase II clinical trial of one fraction of 19Gy or two fractions of 13.5Gy. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 122, 87-92. doi: 10.1016/j.radonc.2016.10.019

Nagore, G., Lopez Guerra, J. L., Krumina, E., Lagos, M., Ovalles, B., Miro, A., . . . Gomez-Iturriaga, A. (2018). High dose rate brachytherapy for prostate cancer: A prospective toxicity evaluation of a one day schedule including two 13.5Gy fractions. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 127, 219-224. doi: 10.1016/j.radonc.2018.03.022

Patel, S., Demanes, D. J., Ragab, O., Zhang, M., Veruttipong, D., Nguyen, K., . . . Kamrava, M. (2017). High-dose-rate brachytherapy monotherapy without androgen deprivation therapy for intermediate-risk prostate cancer. Brachytherapy, 16, 299-305. doi: 10.1016/j.brachy.2016.11.002

Potharaju, M., Subramanaiam, R., Venkataraman, M., Perumal, K., Ramakrishnan, B., Vangara, R., & Reddy, S. (2015). A Report on the Clinical Outcome after High-Dose Rate (HDR) Brachytherapy as Monotherapy in Early Prostate Cancer. Cureus, 7, e303. doi: 10.7759/cureus.303

Prada, P. J., Cardenal, J., Blanco, A. G., Anchuelo, J., Ferri, M., Fernandez, G., . . . Fernandez, J. (2016). High-dose-rate interstitial brachytherapy as monotherapy in one fraction for the  treatment of favorable stage prostate cancer: Toxicity and long-term biochemical results. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 119, 411-416. doi: 10.1016/j.radonc.2016.04.006

Ragab, O., Banerjee, R., Park, S.-J., Patel, S., Zhang, M., Wang, J., . . . Kamrava, M. (2018). Comparison of patient-reported acute urinary and sexual toxicity scores in a 6- versus 2-fraction course of high-dose-rate prostate brachytherapy monotherapy. Journal of medical imaging and radiation oncology, 62, 109-115. doi: 10.1111/1754-9485.12648

Raleigh, D. R., Chang, A. J., Tomlin, B., Cunha, J. A., Braunstein, S. E., Shinohara, K., . . . Hsu, I.-C. (2015). Patient- and treatment-specific predictors of genitourinary function after high-dose-rate monotherapy for favorable prostate cancer. Brachytherapy, 14, 795-800. doi: 10.1016/j.brachy.2015.06.004

Yang, G., Strom, T. J., Wilder, R. B., Shrinath, K., Mellon, E. A., Fernandez, D. C., & Biagioli, M. C. (2015). Dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with high-dose-rate brachytherapy for large prostate volumes. International braz j urol : official journal of the Brazilian Society of Urology, 41, 435-441.

Yoshida, K., Yamazaki, H., Nakamara, S., Masui, K., Kotsuma, T., Akiyama, H., . . . Yoshioka, Y. (2014). Comparison of common terminology criteria for adverse events v3.0 and radiation therapy oncology group toxicity score system after high-dose-rate interstitial brachytherapy as monotherapy for prostate cancer. Anticancer research, 34, 2015-2018.

Yoshioka, Y., Nose, T., Yoshida, K., Oh, R. J., Yamada, Y., Tanaka, E., . . . Inoue, T. (2003). High-dose-rate brachytherapy as monotherapy for localized prostate cancer: a retrospective analysis with special focus on tolerance and chronic toxicity. International journal of radiation oncology, biology, physics, 56, 213-220.

Zamboglou, N., Tselis, N., Baltas, D., Buhleier, T., Martin, T., Milickovic, N., . . . Tunn, U. W. (2013). High-dose-rate interstitial brachytherapy as monotherapy for clinically localized prostate cancer: treatment evolution and mature results. International journal of radiation oncology, biology, physics, 85, 672-678. doi: 10.1016/j.ijrobp.2012.07.004